Chromosome Study Leads to Counseling Pregnant Women

Fetuses with a so-called new balanced chromosomal aberration have a higher risk of developing brain disorders such as autism and mental retardation than previously anticipated and the risk is 20% for fetuses with these types of aberrations.

These chromosomal aberrations are seen in the fetus in one out of 2,000 pregnant women. Until now, when such an aberration has been found, the medical doctors have told the pregnant woman that the fetus' risk of developing congenital malformations is 6% to 9%.


Scientists from the University of Copenhagen (Copenhagen, Denmark) performed long-term follow-up (mean 17 years) of a registry-based nationwide cohort of 41 individuals carrying a prenatally detected de novo balanced chromosomal rearrangements (BCR) with normal first trimester screening/ultrasound scan. In Danish hospitals the method of classical chromosomal analysis, where the genetic material is examined in a microscope, is increasingly being replaced with another method, chromosomal microarray.

The team examined the Danish health records to find everyone born with a de novo balanced chromosomal aberration since 1975. Each time they found a person with the aberration, they established a control group of five individuals with normal chromosomes, who had been born more or less at the same time by a mother of the same age. They then visited the majority of the persons to do a health examination and collect blood samples for modern genetic analyses. By comparing the health data of the group with the chromosomal aberrations and the control group, the scientists found two-three times higher risk of developing a neurocognitive disorder in the group with the chromosomal aberrations.

The scientists observed a significantly higher frequency of neurodevelopmental and/or neuropsychiatric disorders than in a matched control group (19.5% versus 8.3%), which was increased to 26.8% upon clinical follow-up. Chromosomal microarray of 32 carriers revealed no pathogenic imbalances, illustrating a low prognostic value when fetal ultrasound scan is normal. In contrast, mate-pair sequencing revealed disrupted genes (ARID1B, NPAS3, CELF4), regulatory domains of known developmental genes (ZEB2, HOXC), and complex BCRs associated with adverse outcomes. The team found that the new whole genome sequencing techniques are much better than any other techniques at assessing the health effect of a balanced chromosomal aberration.

Iben Bache, MD, PhD, an associate professor of Clinical Genetics, and senior author of the study said, “We have not known which analyses to use to discriminate the fetuses that will be healthy from those that will eventually develop disorders. Our study shows that by using the new sequencing technologies we can in fact discriminate in a number of cases. This may greatly affect the diagnosing and counseling of pregnant women carrying fetuses with this specific type of chromosomal aberration in the future.” The study was published on May 24, 2018, in the American Journal of Human Genetics.

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